Category Archives: C. difficile Treatment Clinical Studies

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REBIOTIX

Phase 3 Clinical Trial of RBX2660 for the Prevention of

Recurrent Clostridium difficile Infection

Phase 3 Initiation Advances Development of Lead Microbiome-based Drug, RBX2660, Following Completion of Three Separate Phase 2 Trials

Rebiotix Inc., a clinical-stage microbiome company focused on harnessing the power of the human microbiome to treat challenging diseases, announced today that it has enrolled the first patient in a Phase 3 clinical trial of RBX2660 for the prevention of recurrent Clostridium difficile (C. diff) infection.

RBX2660 is Rebiotix’s most clinically advanced drug product developed from the company’s Microbiota Restoration Therapy™ (MRT) platform. MRT is a standardized, stabilized drug technology that is designed to deliver a broad consortium of spore and non-spore forming microbes into a patient’s intestinal tract to restore a dysbiotic gut to a healthier state.

The randomized, double-blind, placebo-controlled Phase 3 clinical trial will evaluate the efficacy and safety of RBX2660 for the prevention of recurrent Clostridium difficile (C. diff) infection. The primary endpoint of the trial compares the proportion of subjects with treatment success following a blinded treatment with RBX2660 compared to the blinded placebo arm. Treatment success is defined as preventing recurrent C. diff infection for eight weeks. The multicenter Phase 3 clinical trial of RBX2660 will be conducted in the United States and Canada and is designed to support a Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA).

“Patients with debilitating, recurrent C. diff need solutions. We plan to continue our strong momentum generated by our Phase 2 results in this Phase 3 trial as we seek to advance RBX2660 toward registration and potential approval so patients have an option for this unmet medical need,” said Ms. Lee Jones, President and CEO of Rebiotix. “Initiating the Phase 3 clinical study of RBX2660 is a significant milestone for Rebiotix and showcases the potential of our Microbiota Restoration Therapy™ (MRT) platform to enable the development of microbiome-directed drug products.”

“It’s exciting to see RBX2660 begin a Phase 3 trial for recurrent C. diff infection,” said Dale Gerding, MD, MACP, FIDSA, Professor of Medicine at Loyola University Chicago and Chief Medical Officer of Rebiotix. “This disease is especially challenging to treat and having this microbial therapy available to physicians could dramatically change how we manage the vexing problem of recurrences of this leading healthcare-associated infection.”

RBX2660 is the first drug product in clinical study from the Microbiota Restoration Therapy (MRT) platform The initiation of the Phase 3 clinical trial follows a Phase 2 program that evaluated the safety and efficacy of RBX2660 for the prevention of recurrent C. diff infection. The Phase 2 program consisted of three separate Phase 2 studies, including a randomized, double-blind, placebo controlled Phase 2b trial. The drug has been tested in approximately 300 patients with many followed to 24 months post treatment. Rebiotix is also advancing RBX7455, a lyophilized, room-temperature stable, oral capsule formulation of its MRT technology in an investigator sponsored Phase 1 study

For more information on Rebiotix and its pipeline of human microbiome directed therapies, visit

Vitality Biopharma, a corporation dedicated to the development of cannabinoid prodrug pharmaceuticals, and to unlocking the power of cannabinoids for the treatment of serious neurological and inflammatory disorders, today announced that it has obtained positive results demonstrating antimicrobial activity of cannabinoids and filed for patent protection on the use of cannabinoid compounds for the treatment of microbes including Clostridium difficile and other “superbug” pathogens.

Utilizing a list of the top drug-resistant pathogens from the United States Centers for Disease Control and Prevention (CDC), Vitality researchers screened for antimicrobial activity in their portfolio of compounds. Vitality Biopharma discovered new antimicrobial activities for cannabinoids, and as a result has filed for patent protection on the use of cannabinoids and cannabinoid prodrugs for the treatment of multiple pathogenic bacterial infections.

At the top of the CDC’s list is Clostridium difficile (C. diff), which is classified as an urgent threat to human health. The CDC reported in 2015 that it infected almost 500,000 Americans and was directly responsible for 15,000 deaths. Vitality successfully demonstrated antimicrobial reactivity of a cannabinoid against C. diff, and is currently conducting follow-on studies designed to enable pharmaceutical use of their targeted cannabinoid prodrugs for this application.

The Company also confirmed that cannabinoids have antimicrobial activity towards methicillin-resistant Staphylococcus aureus (MRSA), a pathogen that was recently listed on the World Health Organization’s (WHO) list of priority pathogens that pose a significant threat to human health globally. Additional antimicrobial activity was seen towards other antibiotic-resistant bacterial species that were included on the CDC and WHO lists, and Vitality is seeking broad intellectual property coverage for use of cannabinoids against these pathogens as well.

“Our cannaboside prodrugs enable the targeted delivery of cannabinoids into the large intestine, where C.diff infections colonize, take over, and can cause severe damage. Our compounds are uniquely suited for performing this task, and it’s now clear they may provide benefits to gut health through multiple mechanisms.” said Dr. Brandon Zipp, Director of R&D at Vitality. Robert Brooke, the Company’s CEO, adds that, “This is a logical extension of our work that has been focused on gastrointestinal disease, and represents a new opportunity to treat a serious and life-threatening condition.”

Article Summary:

Background

Clostridium difficile infection is the most common health-care-associated infection in the USA. We assessed the safety and efficacy of ridinilazole versus vancomycin for treatment of C difficile infection.

Methods

We did a phase 2, randomized, double-blind, active-controlled, non-inferiority study. Participants with signs and symptoms of C difficile infection and a positive diagnostic test result were recruited from 33 centres in the USA and Canada and randomly assigned (1:1) to receive oral ridinilazole (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days. The primary endpoint was achievement of a sustained clinical response, defined as clinical cure at the end of treatment and no recurrence within 30 days, which was used to establish non-inferiority (15% margin) of ridinilazole versus vancomycin. The primary efficacy analysis was done on a modified intention-to-treat population comprising all individuals with C difficile infection confirmed by the presence of free toxin in stool who were randomly assigned to receive one or more doses of the study drug. The study is registered with ClinicalTrials.gov, number NCT02092935.

Findings

Between June 26, 2014, and August 31, 2015, 100 patients were recruited; 50 were randomly assigned to receive ridinilazole and 50 to vancomycin. 16 patients did not complete the study, and 11 discontinued treatment early. The primary efficacy analysis included 69 patients (n=36 in the ridinilazole group; n=33 in the vancomycin group). 24 of 36 (66·7%) patients in the ridinilazole group versus 14 of 33 (42·4%) of those in the vancomycin group had a sustained clinical response (treatment difference 21·1%, 90% CI 3·1–39·1, p=0·0004), establishing the non-inferiority of ridinilazole and also showing statistical superiority at the 10% level. Ridinilazole was well tolerated, with an adverse event profile similar to that of vancomycin: 82% (41 of 50) of participants reported adverse events in the ridinilazole group and 80% (40 of 50) in the vancomycin group. There were no adverse events related to ridinilazole that led to discontinuation.

Interpretation

Ridinilazole is a targeted-spectrum antimicrobial that shows potential in treatment of initial C difficile infection and in providing sustained benefit through reduction in disease recurrence. Further clinical development is warranted.

Funding

Wellcome Trust and Summit Therapeutics.

To read the article in its entirety, please click on the following link:

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